Tuesday, August 31, 2010

We are too readily seduced by what is going on in the blood in CLL. The real deal is what is happening in the lymph nodes. Like in other cancers, a major factor in the progression of the disease is the formation of new blood vessels. In last week's Blood a paper from Italy explores the relationship between blood levels of Angiopoietin-2 and prognosis. Angiopoietin-2 is a glycoprotein which destabilizes blood vessels causing them to revert to a more plastic state and making them more succeptible to the effect of vascular endothelial growth factor (VEGF). It is secreted by CLL cells, especially those that are CD38 positive. unsurprisingly, this paper finds that high levels of Angiopoietin-2 correlate with a poor prognosis.

My friend and colleague, Steve Devereux, suggested to me a couple of years ago that CLL might benefit from treatment with Avastin. Alas, he couldn't raise a grant to study the question, but this is further evidence that he may have been right.

HARVARD University has confirmed that it has found evidence of misconduct by Marc Hauser, one of the leading lights in the field of animal cognition.

In a letter to Harvard researchers on 20 August, dean of arts and sciences Michael Smith said that Hauser was “solely responsible” for eight instances of scientific misconduct. Three were in papers already identified as targets for a three-year probe by the university. The other five were in studies corrected before being published or which did not lead to papers.

The letter says that “there were problems involving data acquisition, data analysis, data retention, and the reporting of research methodologies and results”. Harvard says it has moved to “impose appropriate sanctions”, but does not say what they are.

Following Harvard's announcement, Hauser also commented for the first time. “I am deeply sorry for the problems this case has caused to my students, my colleagues, and my university,” he wrote, in a statement emailed to New Scientist.

Federal agencies that provided grants for Hauser's work and the US Attorney for the District of Massachusetts are still investigating.

Saturday, August 28, 2010

In 2008 the Archbishop of Canterbury was quoted as saying, "There is a place for finding what would be a constructive accommodation with some aspects of Muslim law, as we already do with some other aspects of religious law."

Suhaib Hasan, Secretary General of the Islamic Sharia Council, has stated, "If Sharia law is implemented, then you can turn this country (the UK) into a haven of peace because once a thief's hand is cut off nobody is going to steal. Once, just only once, if an adulterer is stoned nobody is going to commit this crime at all. We want to offer it to the British society. If they accept it, if they accept it, it is for their good and if they don't accept it they'll need more and more prisons.

Just imagine if a revered cleric had made the Archbishop's statement in Saudi Arabia or Pakistan, substituting the word 'Christian' for 'Muslim'. Would the revered cleric's head still be in contact with his body?

Just imagine if the Archbishop had made Suhaib Hasan's statement in the UK. He would have been pilloried as a Nazi.

Here are some of the tenets of Sharia law. See if you are keen for any to be adopted.

In the Civil code:A woman's testimony is worth only half of a man's; though in some sharia cases it is completely unacceptable.A man can have four wives and can divorce his wife by a simple declaration.A woman can have only one husband at a time and must give justifications for requesting a divorce, some of which are extremely difficult to prove.The father regains custody of his children when they reach a certain age, or sooner if the woman remarries.Sons are entitled to double inheritance compared to daughters.

In the Penal code:Married adulterers are to be stoned to death.Theft is punishable by amputation.Drinking alcohol is punishable by flogging.Highway robbery is punishable by crucifixion.Apostasy (leaving Islam) is punishable by death. Although some schools believe that this does not apply to women and children, all schools believe it applies to adult males.Homosexual behaviour is punishable by death.Eating during daytime during Ramadan is punishable by imprisonment or flogging.Improper veiling of a woman is punishable by fines, imprisonment or threats.

The pressure to introduce Sharia law into Britain is being opposed by a Human Rights group, One Law for All who have issued a report, Sharia Law in Britain: A threat to One Law for All and Equal Rights.

As the report states: Sharia law is practiced in Britain primarily by Sharia Councils and Muslims Arbitration Tribunals. Both operate on religious principles and are harmful to women although Muslim Arbitration Tribunals are wrongly regarded as being of more concern because they operate as tribunals under the Arbitration Act 1996, making their rulings binding in law.

Sharia Councils, on the other hand, claim to mediate on family issues but in practice often this differs little from arbitration: they frequently ask those appearing before them to sign an agreement to abide by their decisions; they call themselves courts, and the presiding imams, judges. Their decisions are then imposed and regarded as having the weight of legal judgements.

There is neither control over the appointment of “judges” in Sharia Councils or Tribunals nor an independent mechanism for monitoring them. Clients often do not have access to legal advice and representation. The proceedings are not recorded, nor are there any searchable legal judgements, nor any real right of appeal.

Sharia law cannot be compared to secular legal systems because it is considered sacred law that cannot be challenged. There is no scope to look at the interests of the individuals involved, as required by UK family law.

These legal processes ignore both common law and due process, far less Human Rights, and provide little protection and safety for women in violent situations.

There is a general assumption that those who attend Sharia courts do so voluntarily and that unfair decisions can be challenged in a British court. Many of the principles of Sharia law are contrary to British law and public policy, and would in theory therefore be unlikely to be upheld in a British court. In reality, however, women are often pressured by their families into going to these courts and adhering to unfair decisions, and may lack knowledge of English and their rights under British law. Moreover, refusal to settle a dispute in a Sharia court can give rise to threats and intimidation, or at best being ostracised.

According to Maryam Namazie, spokesperson of the One Law for All Campaign and an author of the report, “The existence of a parallel legal system that is denying a large section of the British population their fundamental human rights is scandalous. Our findings show that it is essential to abolish all religious courts in the UK. Their very existence and legitimisation puts pressure on vulnerable women not to assert their civil rights in a British court. As long as Sharia Councils and Tribunals are allowed to continue to make rulings on issues of family law, women will be pressured into accepting decisions which are prejudicial to them and their children.”

Richard Dawkins is certainly no favourite of mine but even he laments the decline of Christianity in this country. I quote, "There are no Christians, as far as I know, blowing up buildings. I am not aware of any Christian suicide bombers. I am not aware of any major Christian denomination that believes the penalty for apostasy is death. I have mixed feelings about the decline of Christianity, insofar as Christianity might be a bulwark against something worse."

Friday, August 27, 2010

There is no doubt that rituximab was the drug of the decade as far as sufferers from lymphoid malignancies are concerned, but the big question is why does it work? After all, I spent nearly thirty years testing monoclonal antibodies as treatments for lymphoma with very disappointing results. Studies using anti-idiotype, anti-CD5, anti-CD19, anti-CD22, anti-CD23 and anti-CD37 were all very disappointing, but by a lucky chance the anti-CD20s were effective. Why?

We know that the CD20 molecule is an unusual one, but there is one loop that stands out from the cell surface, though it never gets far from the surface. It is against this loop that most of the antibodies (including rituximab) react. There is a much smaller loop (on the left in the diagram) that hardly protrudes from the surface at all and it is against this that the antibody ofatumumab reacts.

My ex-colleagues in Southampton, Mark Cragg and Martin Glennie have been beavering away at this topic for years and in three recent papers that have described what they think is going on (Lim et al Haematologica 2010; 95:135-143; Beers et al Blood 2010; 115:5191-5201; and Beers et al Semin Hematol 2010; 47:107-114.). In this article I will try to distill what they have discovered into simple language.

Simply binding an antibody to a leukemia cell isn't enough to kill that cell. Usually some sort of effector mechanism is necessary to kill the cell. When we experiment with B cells and antibody in a test tube, it becomes apparent that there are a number of means of killing those cells. The easiest to demonstrate is Complement Dependent Cytotoxicity (CDC). Complement is a series of proteins labelled C1 to C9 which form a cascade of reactions eventually ending up by punching holes in the target cell. When you have a blood transfusion and get the wrong blood group it is CDC that destroys your blood cells (and may kill you), but it is not clear that this is an important mechanism inside the body even if it does work in the test tube.

You can destroy Complement by heating serum to 56 degrees Celsius or in an animal by injecting Cobra Venom Factor. In this way you can determine whether CDC is an important mechanism. In general terms, most investigators do not think it is an important mechanism in human antibody therapy.

Not all anti-CD20 antibodies permit CDC and Cragg and Glennie have divided monoclonal anti-CD20s into those that do (Type I) and those that don't (Type II). Rituximab is a Type I antibody. Type I antibodies have other characteristics, chief of which is to redistribute CD20 into lipid rafts which are then internalized, thus clearing the antigen from the surface. This process is known as antigenic modulation, which I have written about earlier.

There was much confusion about antigenic modulation, and it has always been said that CD20 is one of the few antigens that doesn't modulate, which is why antibodies against it work so well. That turns out to be true for some types of lymphocytes and not for others. Cells from diffuse large B-cell lymphoma and from follicular lymphoma and from some lymphoblastoid cell lines are poor at antigenic modulation, whereas other cell lines and cells from mantle cell lymphoma are much better at it. Best of all are CLL cells. Normal B cells are also good modulators.

Antigenic modulation is distinct from antigen shaving in which the antigen/antibody complex is skimmed from the surface of the malignant B cell by macrophages, usually in the spleen. With antigenic modulation the antibody is internalized by the malignant B cells. Note that both these mechanisms consume the monoclonal antibody and may account for the more rapid than expected clearance of antibody from the circulation.

Most people believe that the most important method of killing that rituximab uses is ADCC which stands for Antibody Dependent Cellular Cytoxicity. This process uses other cells (either NK cells or macrophages) to kill the tumor cell. When the antibody latches on to the CD20, the other end of the molecule sticks out away from the cell surface. This is known as the Fc portion of the molecule (the name comes from the 1950s when immunoglobulin molecules were broken up by various chemicals; the Fc portion was the fraction that could be crystalized). NK cells and macrophages have receptors that recognize Fc (called Fc receptors and labelled CD16, CD32 and CD64). Certain individuals have minor molecular variations (polymorphisms) of CD16 and CD32 which make their Fc receptors less effective. If these people get follicular lymphoma then rituximab works less well than in people without the polymorphisms. However these polymorphisms do not affect the outcome of CLL patients treated with FCR, suggesting that rituximab may act differently in CLL.

However, Complement activation may still be important. It seems likely that activation of Complement is the cause of the acute 'allergic' reaction caused by the first dose of rituximab, which is especially bad where there is a high white count. It is my opinion that the anaphylactoid fragments of Complement, C3a and C5a are responsible. Furthermore, there is evidence that both C3b and C5b inhibit ADCC.

What about Type II antibodies? There aren't very many. The best known is tositumomab, the antibody that is labelled with radioactive iodine in Bexxar. These antibodies do not activate complement and do not push CD20 into lipid rafts. Neither do they cause antigenic modulation. But do they kill tumor cells? They can certainly activate ADCC, but they also have another mechanism of cytotoxicity. This form of killing involves homotypic adhesion, which simply means that two tumor cells stick together. It is known that the process requires cholesterol and is energy dependent. It involves mitochondria moving within the cells to the area where they are in contact. Cell death is caspase independent, which means that it doesn't use apoptosis and is therefore likely to be effective in p53 deficient tumors. The killing requires lysosomes which swell and release their contents into the cytoplasm and extracellular space. Lysosomes are spherical organelles that contain enzymes (acid hydrolases) that break up endocytized materials and cellular debris. If they release their enzymes into the cytoplasm, it's like letting a tiger out of its cage. Something's going to die - in this case, the cell.

Of the new antibodies available in the clinic or in trials, ofatumumab is a Type I antibody whose ability to stay on the surface (because it goes for the little loop, not the big one) for a long time negates the negative effect of antigenic modulation. On the other hand, GA101 is a type II antibody. It has good direct cell killing and its Fc has been optimized by adding the correct sugars to the amino acids so that ADCC has been improved.

Wednesday, August 25, 2010

I rang the oncologist yesterday and we agreed that I postpone my appointment with him until I have seen the surgeon at the end of next month. I will have a CT scan midway through September.

My weight is gradually creeping back up - I am now 182 pounds having been 200 before the operation and 177 at my lowest. I still get a bit of colic and I take antispasmodics, but on the whole my anastomosis is working fine. Most evenings I feel quite bloated by bedtime. My strength is returning and I no longer need an afternoon nap. I am driving short distances - my first trip to the bank this morning and I polished the wood block floor that extends through most of the ground floor of out house today. I plan to attend a lecture in Southampton next week. This will entail a 60 mile round trip in the Jaguar.

I hope that I might be fit enough to attend the UKCLL Forum meeting in London in September.

I have restarted editing Leukemia Research and am refereeing for Blood and British Journal of Haematology.

The CT scan and appointment with the oncologist will determine whether I am to have further chemotherapy

Monday, August 23, 2010

I am grateful to correspondent,Lynn, for drawing attention to something that had passed me by while I was ill. In distinguishing between iron deficiency and the anemia of chronic disorders, it is usually sufficient to measure the serum iron, the total iron binding capacity and the serum ferritin. In both, the serum iron will be low, but the iron binding capacity goes up in iron deficiency and down in the anemia of chronic disorders. Serum ferritin goes down in iron deficiency and is normal or raised in chronic disorders.

Sometimes patients have both iron deficiency and a chronic disorder, so how do you decide whether they should be given iron?

A few years ago the serum soluble transferrin receptor assay became available. This goes up in iron deficiency but is unaffected by chronic disorders.

However, this is not true for some hematological malignancies, especially for CLL. The serum soluble transferrin receptor level goes up in CLL and indeed is a measurement of tumor burden. So if you really are not sure whether someone with CLL is also iron deficient and the other tests won't help you, then the only way to find out for sure is to do a bone marrow biopsy and stain it for iron.

Sunday, August 22, 2010

Rose Tremain's novel The Road Home tells the story of an Eastern European immigrant to England. He finds that the streets of London are not paved with gold, that £20 a day is not enough to live on and that Englishmen are not tall, ascetic and witty, fellows with bowler hats and umbrellas, but mostly denizens of the Commonwealth and fat. Reduced to sleeping in doorways, he takes jobs delivering fliers for a kebab stall, picking asparagus in Lincolnshire and washing dishes in a smart restaurant. The people he meets include an Irish drunk, a couple of Chinese homosexuals, a curmudgeonly farmer, a sweet old lady abandoned to a residential home by uncaring children, and many from the London art scene whom Tremain lampoons for their being dressed in the Emperor's New Clothes. Lev, the immigrant, has just lost his wife to leukemia and is emotionally stifled because of this, yet he manages to negotiate his way through the minefield to a happy ending.

No such happy ending for Marcus Trescothick. I am not normally a fan of sporting biographies, but this one is a bit different. Coming back to me tells the story of England's opening batsman, who at the height of his success succumbs to an acute anxiety neurosis. It makes him unable to tour other countries and signals the end of his career as an international cricketer. Frankly I could do with out the, "I scored 47 and 63 in the two innings at Lords but after that I reached my highest test score against the Bangladeshis of 197 at Edgbaston." You can skip all that; just take it for read that he was a very good batsman. What is interesting is how he handled the anxiety and depression and how unaware the cricket management were of the problem. The press were vile, assuming that the problem was a sexual peccadillo of him or his wife.

I liked the explanation given to him by his counsellor. "Depressive illness, caused by stress, nearly always happens to one sort of person. He or she will have the following characteristics; moral strength, reliability, diligence, strong conscience, strong sense of responsibility, a tendency to focus on the needs of others before one's own, sensitivity, vulnerability to criticism, and self-esteem dependent on the evaluation of others. This person is the sort to whom you would turn if you had a problem to sort out upon which your house depended, a safe pair of hands you can trust with your life, though often taken somewhat for granted. People are very surprised when he gets ill; indeed he is the last person you would expect to have a breakdown."

In the 1980s I was very interested in scientific fraud which was then rife in the Ivy League institutions in America. I wrote an article, Fake! , which details the many frauds that were then revealed. The article is available for free if you want to download it. At about the same time New Scientist published a cartoon which showed an old tramp playing a violin for pennies on a street corner with a caption which read, "He learned his trade fiddling at Harvard."

Another Harvard fraud has apparently now surfaced. It concerns the psychologist Marc Hauser who is on a year's leave of absence while the dodgy data are investigated. Hauser's research focuses on the evolutionary roots of the human mind. In a letter he wrote to colleagues, he described the inquiry as painful. The letter said that his lab has been under investigation for three years by a Harvard committee, and that evidence of misconduct was found. He alluded to unspecified mistakes and oversights that he had made, and said he will be on leave for the upcoming academic year.

According to the Boston Globe, "Hauser’s work falls at the intersection of psychology, evolutionary biology, and neuroscience, and he has studied everything from the cognitive and evolutionary underpinnings of language to the idea that morality is innate. He began teaching at Harvard in 1992 and several times has been voted one of Harvard’s most popular professors by graduating students, according to his CV. He is writing a book titled 'Evilicious: Explaining Our Evolved Taste for Being Bad.’"

"A paper in the journal Cognition has been withdrawn. The paper tested cotton-top tamarin monkeys’ ability to learn generalized patterns, an ability that human infants had been found to have, and that may be critical for learning language. The paper found that the monkeys were able to learn patterns, suggesting that this was not the critical cognitive building block that explains humans’ ability to learn language. In doing such experiments, researchers videotape the animals to analyze each trial and provide a record of their raw data. The Harvard investigation, said video records and field notes of one of the co-authors were incomplete. The investigation also raised questions about two other papers co-authored by Hauser. The journal Proceedings of the Royal Society B published a correction last month to a 2007 study. Science, another top journal, was notified of the Harvard investigation in late June and told that questions about record-keeping had been raised. Science has requested a copy of Harvard’s report of its investigation and will “move with utmost efficiency in light of the seriousness of issues of this type."

This isn’t the first time Hauser’s work has been challenged.

"In 1995, he was the lead author of a paper in the Proceedings of the National Academy of Sciences that looked at whether cotton-top tamarins are able to recognize themselves in a mirror. Self-recognition was something that set humans and other primates, such as chimpanzees and orangutans, apart from other animals, and no one had shown that monkeys had this ability."

"Gordon G. Gallup Jr., a professor of psychology at State University of New York at Albany, questioned the results and requested videotapes that Hauser had made of the experiment. “When I played the videotapes, there was not a thread of compelling evidence — scientific or otherwise — that any of the tamarins had learned to correctly decipher mirrored information about themselves," Gallup said in an interview.""

What strikes me now and what struck me in 1981 was how many of these frauds seem to concern evolution. Starting with Piltdown Man, scientists have fabricated data so as to get out from under a creator God. If we have been created by God then we owe him submission and obedience, something that modern man can't abide.

Saturday, August 21, 2010

When I was a medical student there was a fellow student who stood out by being older. He was a dentist who had decided to retrain as a doctor to fulfil his ambition of becoming a facio-maxillary surgeon. He was in his thirties, drove a smart car and always had money that the rest of us couldn't imagine. He had an expression that he used whenever any of the year behaved as 'medical students' (drinking, partying, going to bed at dawn). He would murmur with disdain, "Top two per-cent."

What he was getting at was the fact that the exam system weeded out those with the top two per-cent of IQs to go to medical school. However, having a higher yet IQ doesn't win you any coconuts. You need a certain threshold IQ (say 120), but above that, other things mater for success in life.

Christopher Langan, with an IQ of 200, (my IQ is apparently 163 according to my parents; Einstein's was only 150) is supposed to be the cleverest man in America. He came to fame as a winner on the TV show One versus One Hundred. From a very young age he read and re-read ever more complicated books. He put in the 10,000 hours required to make himself an expert. Ask him anything and he has the answer.

Yet Chris Langan is a failure in life. He has never achieved anything of note during his lifetime (apart from winning quiz shows). He has twice dropped out of College. His background was terrible. His mother had four boys with four different fathers. The man who stayed with her longest was a drunk who beat up both mother and children. He won a scholarship, but lost it because his mother was too indolent to fill in the forms. He lived in poverty which caused him to miss classes and he was insufficiently persuasive with the college administration for them to make allowances for him despite his high intellect.

Robert Oppenheimer was a similar child prodigy, but he came from a privileged background. There were books at home, intellectual conversation, and a social mores that taught you how to behave. He went to Harvard and the as a PhD student to the other Cambridge University in England. In England he deliberately tried to poison his tutor, Patrick Blackett (who would later win the 1948 Nobel prize for physics). Oppenheimer was carpeted, but after protracted negotiations he was put on probation and booked into sessions with a Harley Street psychiatrist; not the usual punishment for attempted murder in England (which at that time retained the death penalty).Later, Oppenheimer went on to head up the Manhattan project which produced the first two nuclear devices. He was a long-shot for this post. He was just 38, junior to many of the scientists he would have to manage. He was a theorist in a job that called for experimenters and engineers. He had many communist friends. He had no administrative experience. He was very impractical, he walked about in a funny hat and knew nothing about equipment. one of his colleagues said, "He couldn't run a hamburger stand."

What he did have was charm. He could charm the birds from the trees and his charm worked on General Groves, the rather stiff and disciplinarian engineer whose approval he needed to implement his ideas.

The particular skill that enables you to talk your way out of an attempted murder rap is called by psychologists, 'practical intelligence'. A lot of politicians have it. It includes knowing what to say and to whom, when to say it, and how to say it with maximum effect. Analytical intelligence is largely genetic, but social savvy is a learned behavior. That's where wealth, good schools and privilege come in. You can't improve analytical intelligence much, but you can improve practical intelligence. You can also improve your ability in divergence tests. Here is a test for you. In the 'Comments' write down how many uses you can imagine for a] a brick, and b] a blanket.

The ideas in this article come directly from Malcolm Gladwell's book Outliers

At the risk of being forced to take this posting down, I reprint the whole of an editorial by Michael Baum, the breast cancer specialist, in today's Lancet. I see no reason why it should be hidden behind a paywall.

Homeopath Waives the Rules.

Evidence-free politics was recently on display when the UK's Department of Health rejected a call by the House of Commons Science and Technology Committee to stop funding the use of homoeopathy in the National Health Service (NHS). This it is claimed will emancipate patients to indulge in choice, even though “His [the Secretary of State for Health] position remains that the evidence of efficacy and the scientific basis of homeopathy is highly questionable”.

Using this kind of logic, why not offer astrology on the NHS to help women decide when to induce labour? It beggars belief that a modern NHS that prides itself on evidence-based medicine should fly in the face of the Science and Technology Committee, which concluded that homoeopathy is nothing other than an elaborate placebo and “involves deceiving the patient every time it is prescribed”. Responding to the Committee, Health Minister Anne Milton said: “We believe in patients being able to make informed choices about their treatment, which includes complementary or alternative treatments such as homeopathy”.

So there you have it: the UK Government supports alternative medicine that by its very nature is nearly all an evidence-free zone. So at a time of financial crisis, Health Minister Andrew Lansley has pledged to continue spending more than £4 million a year to capture the support of a vocal minority. My group has just described a new technique for delivering intraoperative radiotherapy for breast cancer that will save women the 6 weeks of traipsing back and forward to the radiotherapy centre. The sum of money to be spent on homoeopathy over a couple of years could open up this service to all the women in England and Wales who need it, while eventually saving the exchequer about £15 million a year. What's the betting that the introduction of this service will have to wait the approval of the UK's National Institute for Health and Clinical Excellence (NICE) while homoeopathy continues to be allowed to creep under that hurdle? As it transpires the Department of Health refuses to ask NICE to investigate homoeopathy. Shame on you, Health Minister.

Friday, August 20, 2010

Of all the incidents that might justify the complaints of Dawkins and Hitchens against religion, the Binding of Isaac is at first sight the greatest.

What would you think of a father who deliberately murdered his son as some sort of religious ritual? Yet Judaism, Islam and Christianity make Abraham's aborted sacrifice of his son a major incident in the individual faiths (though Islam has made it about Ishmael rather than Isaac).

If you met a father behaving like that today, who could blame you for calling child protective agencies? Is this faith or fanaticism? In the past few years we’ve seen more than enough people who measure their devotion by their willingness to kill defenseless people. In New York, London, Madrid and Bali we can point the finger at fanatical Islamists, but what about Jonesville and Waco? What about Orissa? Moreover, Muslims, Jews and Christians can find examples in their scriptures to justify that kind of ruthlessness.

In the Jewish view, God was testing Abraham, establishing the depth of the commitment upon which the nation of Israel would be founded. No sooner had Abraham arranged the firewood on the altar, taken the knife and stretched out his hand to slaughter his son, than "an angel of God called out to him from the heavens... 'Lay not your hand upon the lad, neither do anything to him; for now I know that you fear God, as you have not withheld your only child from Me... Thus I shall bless you, and multiply your descendants as the stars of the heaven, and as the sand that is at the shore of the sea...' "

Maimonides, the preeminent Jewish expositor of the twelfth century, explains that the "binding of Isaac" served to establish two key axioms of the Jewish faith: a) the extent of man's capacity to love, fear and serve God; b) the principle of "prophecy" - the fact that God communicates His will to man.

By binding Isaac upon the altar, Abraham demonstrated that man is capable of a love and awe of God that surpasses his every other feeling or commitment. For what greater love is there than the love of a parent for his child? What greater fear is there than a parent's fear for the life of his child? With the binding, Abraham set his commitment to God above these most basic truths of human nature, establishing it as the all-surpassing consideration in the life of man.

The second truth established by the incident is the principle of prophecy.

There are many levels and degrees of human communion with the divine, from the scientist's contemplation of God's creation, to the preacher whose interpretation and exposition of Scripture is guided and molded by divine inspiration. Prophecy, however, is the ultimate divine communication - a revelation that completely transcends the equivocation and subjectivity of its human receiver, so that its truth is absolute, incontestable and immutable. A fundamental principle of the Jewish (and indeed Christian) faith is that God communicates to man in this manner.

When Abraham was told to offer Isaac as a sacrifice to God, this was contrary to everything Abraham was and stood for, contrary to everything he knew and believed about God, and contrary to what God, Himself, had said to him.

Abraham knew and related to God as "the merciful and benevolent One, slow to anger, great in kindness."

According to Jewish tradition, the prohibition of taking a human life is one of the seven basic laws of civilization communicated by God to Adam and Noah (the "Seven Noachide Laws") which Abraham had been laboring for many decades to instill in a world where murder and promiscuity were the staples of religious worship. (For we know that the Canaanites indulged in child sacrifices and the many fertility cults had religious prostitutes as part of their devotions). And God had promised Abraham that Isaac (unmarried and childless at the time of the binding) would father a great nation who would carry on Abraham's work of conveying the truth of the One God to the world.

Certainly, we read in Genesis 9:6 that God tells Noah, "Whoever sheds the blood of man, by man shall his blood be shed; for in the image of God has God made man." Furthermore in Genesis 15:4-5 God tells Abraham "a son coming from your own body will be your heir. " He took him outside and said, "Look up at the heavens and count the stars—if indeed you can count them." Then he said to him, "So shall your offspring be." and in Genesis 21:12 God tells him that "it is through Isaac that your offspring will be reckoned."

So when Abraham heard the words "Take your son... and raise him as an offering," he had many reasons to doubt their divinity, to surmise that not God but some malevolent voice had uttered them in his soul's ears. Had his certainty that God had spoken them been an iota less than absolute, he would not - indeed, could not - have acted on them.

Thus, concludes Maimonides, the binding of Isaac is the ultimate exemplar of the principle of prophecy - that God communicates His will to man in a manner that leaves no doubt as to its origin, meaning, or manner of implementation.

Of course, skeptics will cavil at this. How can a man distinguish the voice of God from the voice of a demon? Or from some weird schizophrenic 'voice'? Is it not a common defence for the murderer to say, "God told me to do it? How can one answer such an objection except to say that from what we read, Abraham was a man who knew the voice of God, who had upped sticks from Ur at God's command, who had believed God when told that he would father a child on a 90-year-old woman and whose belief had been credited to him as righteousness.

Abraham was a man who believed that God worked miracles. For the Christian we have to believe that Abraham believed a greater miracle than an old woman becoming a mother. For we read in Hebrews 11:17-19 - By faith Abraham, when God tested him, offered Isaac as a sacrifice. He who had received the promises was about to sacrifice his one and only son, even though God had said to him, "It is through Isaac that your offspring will be reckoned." Abraham reasoned that God could raise the dead, and figuratively speaking, he did receive Isaac back from death

But more important, for the Christian, this whole episode prefigures the sacrifice of Christ - the doctrine known as substitutionary atonement. God provided a substitute, the ram caught in a thicket. Whereas Abraham is spared from sacrificing his son; God has to sacrifice His son to expunge the sin of His people. Abraham was told to build the alter in the vicinity of Moriah, the very place where Christ was crucified. Abraham figuratively received his son from the grave; Jesus actually rose from the dead.

The aborted sacrifice of Isaac should not act as an example for those who obey God; indeed child sacrifice is roundly condemned in Scripture for example Jeremiah 32:35 They built high places for Baal in the Valley of Ben Hinnom to sacrifice their sons and daughters to Molech (an Ammonite god), though I never commanded, nor did it enter my mind, that they should do such a detestable thing and so make Judah sin.

The important point of the story is that Abraham did not kill his son. God stopped him. Abraham obeyed God. The War Poet Wilfred Owen grieving over so many comrades sent to their deaths needlessly had his own take on the story:

So Abram rose, and clave the wood, and went,And took the fire with him, and a knife.And as they sojourned both of them together,Isaac the first-born spake and said, My Father,Behold the preparations, fire and iron,But where the lamb for this burnt-offering?Then Abram bound the youth with belts and straps,And builded parapets and trenches there,And stretchèd forth the knife to slay his son.When lo! an Angel called him out of heaven,Saying, Lay not thy hand upon the lad,Neither do anything to him, thy son.Behold! Caught in a thicket by its horns,A Ram. Offer the Ram of Pride instead.

But the old man would not so, but slew his son,And half the seed of Europe, one by one.

But this was not what happened. Instead, because the taint remained on mankind God took it on himself to slay his own son. Isaac was a bemused and unwilling sacrifice who needed binding to the alter; Christ knew exactly what he was doing: I lay down my life, he said, no-one takes it from me.

O teach me what it meaneth,That cross uplifted high,With One - the Man of Sorrows-Condemned to bleed and die.O teach me what it cost TheeTo make a sinner whole;And teach me, Savior, teach meThe value of a soul!

This was not an atrocity of God; this was an atrocity of mankind against God.

Tuesday, August 17, 2010

AbstractEvidence is accumulating that in some patients with CLL the expression of ZAP-70 changes over time. This diminishes its role as a prognostic marker but increases our understanding of the pathophysiology of the disease.

CommentaryAlthough the mutational status of the immunoglobulin variable region (IgVH) genes remains the gold standard for prognostic markers in chronic lymphocytic leukaemia (CLL), it is a complicated assay unsuited to routine laboratories. Unfortunately, attempts to find a surrogate have run into several obstacles. CD38 expression measured by flow cytometry was an early contender and initially seemed to have as much predictive value IgVH mutations. Unfortunately, it was subsequently found to give disparate results in 28% and even worse was described as changing over time in 24% (1).

More recently, ZAP-70 expression has attracted great interest. Although transiently expressed during certain stages of B-cell development, most mature peripheral blood B cells do not express ZAP-70, a cytoplasmic tyrosine kinase which is the key signalling molecule for T-lymphocytes and NK-cells. In CLL it acts as an auxiliary molecule for B-cell signalling in the more aggressive cases, probably acting to block inhibitors of signalling through syk. It’s presence in aggressive CLL appears to be due the chaperoning function of heat shock protein 90 (Hsp90). After it was originally identified in gene expression microarrays as a gene differentially expressed in CLL cells with unmutated IgVH genes, several laboratories developed flow cytometric assays that potentially could be used by routine laboratories. Initially, there was 95% concordance with IgVH mutational status, but a later assay using the much more convenient direct immunofluorescence, showed concordance of only 77%, hardly better than CD38, although with this assay ZAP-70 appeared to perform better than IgVH mutations as a prognostic factor (reviewed in 2).

The disparity betweens these assays has prompted a search by several laboratories for an assay that would be reliable, reproducible and of prognostic value. This quest is currently unresolved. The type of anticoagulant to use, allowable storage and transit time, which gating strategy, which monoclonal antibody and which fluorescent dye all remain in dispute and how to express the results is still a contentious issue (3). Nevertheless, several publications have attested to the fact that like IgVH mutations and unlike CD38, ZAP-70 is stable over time.

In today’s issue of Leukemia and Lymphoma, Poulain et al (4) dispute this. Four out of 33 ZAP-70 negative cases subsequently became ZAP-70 positive and this was associated with clinical progression. Two out of 27 ZAP-70 positive patients became negative. In one case this was associated with corticosteroid treatment, a phenomenon that has been observed previously. Although previous publications have reported on the stability of ZAP-70 over time, close scrutiny of these publications confirms that in a small number of patients (around 10%) ZAP-70 expression does change as time passes, although until Poulain et al there has been no indication as to why.

Recently Boelens et al (5) reported that ZAP-70 expression in CLL is higher in lymph node cells than in peripheral blood cells and Cutrona et al (6) demonstrated that within normal germinal centres there is a population of ZAP-70 positive, CD38 positive B cells representing in vivo activated cells.

These observations add to our understanding of ZAP-70 in CLL. It seems likely that both ZAP-70 and CD38 are normal features of activated B cells, rather than markers of neoplastic aberration. In CLL activation events and cell division both take place in proliferation centres and here upregulation of both markers occurs. There seems to be a free exchange of cells between tissue and blood making the presence of both CD38 and ZAP-70 surrogates for the rapidity of cell turnover.

The mutational status of the IgVH genes is fixed in CLL making it unique as a prognostic marker; it assigns cases into one immutable subgroup or the other. Other markers, whether CD38 or ZAP-70 expression or chromosomal abnormalities, can be acquired during the course of the disease. Early stage patients can gain little comfort from knowing that they are not present at diagnosis.

Monday, August 16, 2010

I know it is a major debating point in America, but it is just as much so in the UK. For at least 13 years of Labor government Britain has allowed unfettered immigration with a nod and a wink at the laws of the land. One of the reasons for this has been the growth in the economy started under the Tories in 1995 and continued until 2007 when Gordon Brown was caught with his trousers down. Rather than compelling British layabouts to take work, they were featherbedded by benefits funded by inflation imported from China, while immigrants from Poland, Romania, the Baltic states and Bulgaria were welcomed via their EU status and meantime swathes of people from the Indian sub-continent were admitted as 'students' and family members, all prepared to take poorly paid jobs.

The recession has made the problem worse as jobs have disappeared and more and more benefits claimed; quite apart from the pressure on schools and the NHS that the immigrants bring. Although we do not have the porous southern border that the USA does, it has been relatively easy for visitors to overstay their visas, for bogus marriages to be conducted, for economic migrants to claim asylum and for young men to find ways of crossing the Channel. It would not take Arizona-style laws to close these loopholes, though the European Union remains a thorn in our flesh, especially as countries like Hungary offer passports to various Russians and Moldovans with very tenuous claims to Hungarian citizenship. Heaven help us if Spain offers passports to most of South America. We must certainly close our borders.

After years of not enforcing the law, it would be churlish to turn around to the illegals and kick them out; in any case the European Court would find a way of stopping us. On the other hand to offer an amnesty would just encourage more to come in the hope that they would get one too.

Of all places I found this in USA Today from Richard Land, who is president of the Ethics and Religious Liberty Commission for the Southern Baptist Convention

Immigration reform legislation must:

•Respect the God-given dignity of every person

•Protect the unity of the immediate family

•Respect the rule of law

•Guarantee secure national borders

•Ensure fairness to taxpayers

•Establish a path toward legal status and/or citizenship for those who qualify and wish to become permanent residents.

The government has not controlled the borders. The reality has been that too often, those who desire to enter our country illegally have encountered two apparently contradictory signs at our border: one saying "No Trespassing" and the other saying "Help Wanted."

Once the borders are secure, we should have a grace period where undocumented workers can come forward, register, pay fines and back taxes, undergo a criminal background check, agree to learn to read, write and speak English, and go to the back of the line behind those who have, and are, trying to enter our country legally. Those who do not choose to accept this generous offer should be deported immediately.

This is not amnesty. Amnesty is a pardon, a "free ride," where government forgives your transgressions and pardons it with no obligations or penalties. This proposal would allow undocumented workers to come forward, obtain a probationary state and begin to earn their way to full legal status.

No one is saying that they haven't broken the law and they should not be punished for doing so. The only question is what is to be the nature of the punishment — deportation (which means uprooting huge numbers of people and tearing families apart) or the penalties outlined above.

Sunday, August 15, 2010

Splenic irradiation is the forgotten treatment for CLL. Perhaps it is because there is no profit to be made from it by the drug companies, but for certain individuals there are advantages compared to drug treatment. I should say up front that it is not a cure, but then nothing is short of an allograft. Nor is it likely to produce the very long remissions that are possible with FCR, but there are very many patients for whom FCR is too toxic. But there are some patients for whom splenic irradiation is the ideal treatment and CLL physicians are very resistant to using it.

I first came upon it was a young doctor when it was an option in the MRC CLL 1 and 2 Trials which began in 1978. I was actually a co-author of the report of those trials which were published in 1991 (Catovsky D, Richards S, Fooks J, Hamblin TJ. Leukemia and Lymphoma 1991; Supplement pp 105-112). In CLL 1 the overall survival of patients treated with splenic irradiation was 5 years compared to 3.8 years for those treated with chlorambucil. The numbers were small and did not reach statistical significance, and the dose of chlorambucil was only 40mg/sq m. However in CLL 2 the overall survival for those treated with splenic irradiation was 3.4 years compared to 4.1 years for chlorambucil. Again the difference was not statistically significant. The conclusion that we drew was that splenic irradiation was not an inferior treatment to the dose of chlorambucil used in the original fludarabine trial or the recent alemtuzumab trial.

I am grateful to my friend Stacie who has sent me a 2001 paper that reviews several trials of splenic irradiation (SI) in CLL. It is from a journal that I don't normally read. (Weinmann M, Becker G, Einsele H, Bamberg M. Radiotherapy and Oncology 2001; 58:235-246.)

Of late, SI has only been used in patients with hypersplenism who were considered unfit for splenectomy, even if performed by keyhole surgery. But in the past it was used as a therapeutic modality which attempted to control the disease as a whole rather than that which is localized to the spleen. How it was supposed to work is a bit of a mystery, but it certainly did work, with some patients (22-38%) achieving what was then thought of as a complete remission. There are various theories why it works. One suggested that there is a circulation of all malignant cells through the spleen so that they all get a dose of radiation as they are passing through, but experiments with radiolabelled lymphocytes do not seem to confirm that. Other suggestions are that there is an induced change to the array of lymphocyte subpopulations or to the cytokine environment that has an effect on the survival of CLL cells. However, this is still speculation and we don't really know how it works.

Hypersplenism is the effect that a large spleen has on the neutrophil, platelet and red cell count because of pooling in the spleen or active destruction. If you take the spleen out, these levels return to normal or even overshoot. The same effect can be achieved with splenic irradiation. It is seldom so complete as splenectomy, and it may not be long lasting (remissions of 7-18 months have been reported) but the effect can be repeated, up to four times. One advantage is that with the blood count restored some patients are able to go ahead and have the chemotherapy that they were previously denied because of their low counts.

Apart from restoration of the blood count, SI can shrink a painful or uncomfortable spleen and make substantial inroads into the tumor mass, by reducing white counts and shrinking nodes. The rare 'complete remissions' would not be so defined by modern criteria.

The dose of SI has varied in different trials. In our MRC trials, we used 100 cGy weekly up to a total of 1 Gy, but later studies used larger doses. Typical doses would be 0.5 to 1Gy given daily or 1-3 times a week to a total of 5-10 Gy. Larger doses than this seem to confer no extra benefit.

The most severe side effects seem to have been transient thrombocytopenia and neutropenia and these counts need to be monitored to guard against infection or bleeding. Neither neutropenia nor thrombocytopenia is a contraindication to SI and some patients who are refractory to chemotherapy also respond.

Long term toxicity does not seem to be a major problem, and although radiation does damage T cells, a regimen of carefully titrated doses allows the treatment to be monitored. For many countries in which fludarabine is regarded as expensive and rituximab a wistful dream, SI is a very cheap option for treatment.

Friday, August 13, 2010

Gul and Begum Wazir, from Alum Rock, Birmingham, were reportedly shot after a planned marriage between the couple's daughter and their nephew in Pakistan fell through. Mr Wazir and his family had travelled to the village of Salehana in north Pakistan, which is sometimes referred to as Little Birmingham because of its strong ties with the Pakistani community in the West Midlands.

This is the latest of a long litany of beatings and murder in the name of honor. Harry Potter star, Afshan Azad, was badly beaten by her father Abdul Azad, and his son Ashraf attempted honor killing because of her relationship with a Hindu man.

November 2, '09: Noor Almaleki is dead; run over by her Muslim father for being too "westernized". She lingered for days.

Police in Kingston, Ontario, charged three Montrealers, Mohammed Shafia, his wife Tooba and their 18-year-old son Hamed with mass murder of three of the couple's teenage daughters, including their eldest child, Zainab, 19, and Rona Amir Mohammed, a 50-year-old woman who was Shafia's secret, first wife.

A 15-year-old schoolgirl allegedly murdered for falling in love told her boyfriend that she had been 'tortured' by her father. She was alleged to have been killed by her father Mehmet Goren, after he consulted with his brothers, over her relationship with Halil Unal. A week later Goren plunged an axe into Mr Unal's neck in a desperate bid to restore his family's honor.

A Muslim asylum seeker was sentenced to life in prison after killing his German-born wife because she was 'too independent'. The 27-year-old Kurdish man, identified only as Onder B, was found guilty today of stabbing his wife in the eyes, beating her with a billiard cue and then running over her in his car. His mother-in-law had once told him to be 'strict' with her strong-willed daughter, Mujde - who was also Onder's cousin. On New Year's Eve 2008 he stabbed his 18-year-old wife Mujde 46 times and beat her with a billiard cue. And because she was 'already so disfigured from the stabbing and beating that she would hate me for the rest of her life,' he got into his car and ran over her body several times.

Mohammed Shafii, Hamid Mohammed Shafii and Tooba Mohammad Yahya have been charged with four counts of first-degree murder and four counts of conspiracy to commit murder in Kingston, Canada. The victims were his three teenaged daughters, Zainab Shafia, 19, her sisters Sahari, 17, and Geeti, 13 and a woman originally believed to be their aunt but later found to be a second wife of Shafii, Rona Amir Mohammad. All were found in the family's Nissa Sentra, submerged at the bottom of a Rideau Canal lock near Kingston, Ont. In an interview, Diba Masoomi - a woman described as Mohammad's sister - said that Mr. Shafia "believed his daughter had dishonoured him and the family by having a romance with a young Pakistani man in Montreal." Shafia first married Mohammad in either 1979 or 1980, and then married Yahya in the late 1980s. Both marriages took place in Afghanistan, where it is legal for a man to have more than one wife. The girls were not allowed to go out alone, neither to the cinema nor to meet friends and they were not able to dress freely. Mr. Shafia often criticized the influence of the Western culture on his family since they were not living in an Islamic country anymore.

A terrified wife who predicted her cheating husband would kill her, was stabbed to death by him just days after he was freed in a legal blunder. Sabina Akhtar, 26, went to police in fear of her life after Malik Mannan subjected her to a string of vicious beatings. The taxi driver was jailed for life today at Manchester Crown Court after being convicted of her murder yesterday. He will serve a minimum of 17 years. Speaking outside court, Ms Akhtar's family accused the Crown Prosecution Service of negligence. Her uncle, Reaz Talukder, said his niece would still be alive if her husband had been charged after being arrested for a second time.

Alright, I think you get the picture. But don't think that this is just a Muslim thing. The clash between Western and Islamic culture has highlighted the problem, but it is not the fault of the Koran that this state of affairs exists. The concept of honor will be familiar to all who fought against the Japanese in the Pacific in World War II. It would have been dishonorable for any Japanese soldier to surrender; hence the needless slaughter of a beaten foe. The only reason that it was necessary to drop nuclear bombs on Japanese cities was because of the Japanese sense of 'honor'.

How about those in Britain and France who fought duels because their 'honor' was affronted? And crusaders who went to the Holy Land in order to protect the honor of their God.

Honor killings are common in the Basque country, in Sicily, and especially in Latin America, but of course we are more familiar today when the killer is called Mohammad, Hamid, Masoomi or Shafiri. But supposing we came across a run of honor killings with perpetrators called Turner, Martin or Smith?

Back in the nineteenth century Kentucky was a pretty lawless state. The area of Harlan county in the Appalachians had been settled by eight families in 1819 and between 1860 and 1900 there were more than a thousand murders in the area. Most were down to family feuds, which didn't really stop until the 1930s. The settlers had come from northern Britain, to be precise, the borders between England and Scotland, and even there they had a reputation for feuding.

We have this report from a newspaperman who was called to jury service on one such murder trial in the Twentieth Century. The case before the jury concerned an irascible gentleman who lived next door to a filling station. For several months he had been the butt of various jokes played by the attendants and miscellaneous loafers who hung around the station, despite his warnings and notorious short temper. One morning he emptied both barrels of his shotgun at his tormentors, killing one, maiming a second permanently and wounding a third.

When the jury was polled by the incredulous judge, the reporter was the only one who recorded his vote as guilty. as one of the others put it, "He wouldn't have been much of a man if he hadn't shot them fellows."

What is even more remarkable is an experiment reported by Malcolm Gladwell in his book, Outliers, from the University of Michigan. The experimenters staged a confrontation for psychology students to see how they would respond to an insult. They found that students who came from that part of Kentucky reacted in an aggressive manner while Northerners laughed it off. The culture of honor that originated in the British borderlands in the Eighteenth Century, still persisted in modern day America. Is there any hope for Middle Eastern immigrants?

Perhaps there is. The historian C John Sommerville has shown how Christianity has changed those honor-based cultures of northern Europe in which pride was valued rather than humility, dominance rather than service, courage rather than peaceableness, glory rather than modesty and loyalty to ones own tribe rather than respect for all. This is not the Christianity of the Crusades and the Inquisition, but the Christianity of the Christ who said "Whoever wants to be first must be the servant of all."

The England football manager, Fabio Capello, doesn't speak very good English, so it was probably a misunderstanding that mad him blurt out that it was unlikely that David Beckham would be picked for future England games.

David Beckham has been an England player for about 14 years and was captain for about half that time. He has been idolized by many in the same sort of way that Princess Diana was, though there has been another constituency that has been (and continues) sniping at him in the correspondence columns.

Nevertheless, he is a good example to young men who aspire to footballing greatness. I don't think most people realise how difficult it is to excel at football. The best footballer I ever played with at school, who garnered county, regional and international honours as a schoolboy turned professional and managed to achieve a few seasons with Reading in Division 3 (South).

Beckham was not the best footballer who ever played for England, but there are few if any who showed more enthusiasm for the cause. Whether you are a concert pianist or a brain surgeon it takes 10,000 hours of practice to become an expert in your field. Beckham's expertise was in kicking a football. Remember he featured in a TV advert for Weatabix at the age of 10 doing keepy-upies. Remember that he stayed on after training practising free kicks when the rest of the team went off to the golf course, betting shop or boozer.

The result was that free kick against Greece that stunned the crowd into silence. (And you should not forget that Greece went on to be the next European Champions). Even last season we had an example of Beckham crossing the ball on the volley to make a goal. Remember those two corners that won the European cup in injury time for Manchester United? The stunning long ball to Raul for Real Madrid was typical of his skill and repeated often. Neither Gerrard nor Lampard can rival him in that department.

As a right winger Beckham was neither fast like Walcott nor tricky like Johnson, but by gaining a yard or crossing on the volley he produced an end result that neither of them nor any winger since has produced. His free kicks became a by-word throughout football, and until Ronaldo, no one was better at taking them.

He also kept himself fit. Rooney is already looking dumpy at 23; Beckham has a figure good enough to feature in Gay-mags at 35. People forget that he was London schools cross country champion as a teenager.

Celebrity attaches itself to good footballers - even people like Gareth Southgate. On the whole he has handled it as well as most and has made more money from it. To have done so much without being the best footballer of the century in Britain, demonstrates his ability to make the most of his circumstances.

I can’t say I am much into celebrity culture, but he hasn’t made quite the mess of his life that some of his contemporaries have such as John Terry, Ashley Cole and even Peter Crouch.

Thursday, August 12, 2010

I agree. There is, however, a comprehensive misunderstanding about what the church is about. It is not a museum for saints, but a hospital for sinners. I know plenty of non-religious people with higher moral standards than some Christians. In fact many people from other religions have manifestly higher moral standards than many Christians. It is what you would expect. Muslims frequently live their lives trying to be good enough for Allah. Buddhists and Hindus live lives so as to raise themselves to a higher plane. On the other hand true Christians are people who have realized that they can never be good enough for God.

Christopher Hitchens (who I'm sorry to say is dying from esophageal cancer) wrote a well-known book called God is not Great: How Religion Poisons Everything. He gives as examples the troubles in Belfast, Beirut, Belgrade, Bethlehem and Baghdad. "Religion has been an enormous multiplier of tribal suspicion and hatred," he writes. You have to agree with this. Christian nations institutionalized imperialism, the Inquisition, and the transatlantic slave trade. The totalitarian and militaristic Japanese empire grew out of a culture deeply influenced by Shintoism and Buddhism, Islam is the basis of much of today's terrorism and Hindu nationalists carry out atrocities against both Muslims and Christians in India.

However, such a one-sided view is unfair. Communist Russia, China and Cambodia did everything they could to stamp out all organized religion, yet the Marxists murdered more of their own citizens than any religious organization in history. It seems that this says something about the human condition rather than about any particular religion or philosophy. In 1793 when Madame Roland went to the guillotine on trumped-up charges in the aftermath of the French Revolution. she bowed to the Statue of Liberty in the Place de la Revolution as said, "Freedom, what crimes are committed in your name."

When considered in numerical terms, the Spanish Inquisition was responsible for fewer than 5000 deaths, Joseph Stalin was responsible for more than 20 million, Mao Zedong for 70 million and Pol Pot, more than one and a half million. Adolf Hitler was responsible for perhaps 42 million deaths. Although Germany was ostensibly a Christian country, Hitler despised Christianity and invented his own religion based on blood and race.

Here Hitchens has a problem. Just who is a Christian. Many who call themselves Christians are only nominally so. They perhaps belong to an established church, yet only darken its doors for Christenings, weddings and funerals - the hatch, match and dispatch brigade. Even among those who attend church, perhaps a majority around the world only do so for superstitious reasons. This is often the case in Roman Catholic countries where catechism and confession is the price they pay for belonging. The Irish republic was one such place until the story about the abuse of children by priests became widely publicised, and many South American states are still priest-ridden, with few true believers.

On the other hand there are many who are fanatical about their faith and among these are the most obnoxious individuals; overbearing, self-righteous, opinionated, insensitive and harsh. Jesus called such people Pharisees. Such people may be fanatically zealous and courageous, but they are not fanatically humble, sensitive, loving, empathetic, forgiving and understanding as their supposed leader was. Not much of "Let him who is without sin cast the first stone," about them.

There are many sinners in the New Testament - prostitutes, renegades, sabbath-breakers, collaborators and adulterers - but it is not these whom Jesus condemns, in fact he welcomes them; rather it is the judgemental and condemning Pharisees that he calls names: "You clean the outside of the cup and dish, but inside you are full of greed and wickedness. You neglect justice and the love of God. You load people down with burdens they can hardly carry and you yourselves will not lift a finger to help them." In fact Jesus was only echoing the voice of the prophets before him (Read Isaiah 58:2-7).

It is a fact that people use religion as a lever to gain power of others. In history this has been the role of state churches, whether Catholic, Orthodox, Lutheran or Anglican, and we can see it today with tele-evangelists; and certainly with Ayatollahs. Many atrocities committed in the name of religion were atrocities committed by power hungry men.

The truth is that God is only reached by giving up power. Jesus said, "Whoever wants to be great among you must be your servant, and whoever wants to be first must be servant of all."

Most pre-christian societies were honor/shame based societies. They might have a strict moral code. They might not mug old ladies, but they would not do so because such an act would demean their honor. In contrast a Christian would not mug an old lady because of the harm it would do the old lady and her family - not self-regarding but other-regarding in its motive.

Christians from northern Europe supported the Crusades because they though they were protecting God's honor. Much of how the secular world criticises Christian history stems from the self criticism of Christians.

However bad historical Christianity may have been because it got its wires crossed over what it was supposed to be, there are some historical achievements that Christians should be given credit for. The abolition of the transatlantic slave trade was achieved by Christian activist of the Clapham sect - most famous of them being William Wilberforce, and later the abolition of New world Slavery can be laid at the feet of Christian activists like John Woolman. When the abolitionists were finally at the point of abolishing slavery throughout the British Empire, planters in the colonies foretold that emancipation would cost investors enormous sums of money. The Abolitionists agreed to compensate the slave owners for every freed slave. British people paid a sum equivalent to have the government's budget for 1833.

The Civil Rights movement of the mid-Twentieth Century owes its power to Dr King's invoking God's moral law. He did not say, "Truth is relative and everyone is free to determine what is right and wrong for them." Rather he invoked the prophet Amos, "Let justice roll down like waters and righteousness as a mighty stream."

The undoing of apartheid in South Africa might have resulted in a blood bath had not Christian leaders (however flawed) like Desmond Tutu not set up the Truth and Reconciliation Commission.

The end of communism in Europe had its genesis in Catholic priest Jerzy Popieluszko who was murdered by the Polish secret police. At his funeral 250,000 turned up. Christians marched past the secret police headquarters carrying a banner which read "We forgive".

Or we could think of Archbishop Oscar Romero of El Salvador or Dietrich Bonhoeffer in World War II.

There has been injustice done in the name of Christ, but there are many examples of others throughout history who have been true to the spirit of Christ. And they have done good.

One of the advantages of living in an older house is the possession of a splendid doorbell. I was disappointed therefore to find that people were complaining that when they pressed the bellpush there was no ring. I removed the bellpush and discovered that a wire had snapped. I made an attempt at repair, but it soon became clear that to fix it properly I would have to remove more of the mechanism that I felt able to in my diseased state.

Instead I purchased one of these electronic bells that work on a radio signal. The bell is plugged into an ordinary electric socket and the bellpush screwed to the doorpost without any wiring at all. Now we have the splendid chimes of Big Ben every time anyone rings our bell.

Wednesday, August 11, 2010

You could hardly make it up. All legal attempts to stop it have been exhausted. There will be a mosque built close to the site of the World Trade Center catastrophe.

The building of the Ground Zero mosque has the support of Mayor Bloomberg. The idea is clearly to reach out a hand of tolerance and friendship to the many Muslims who abhor violence and disown the crimes of Bin Laden.

The man behind the mosque is Imam Feisal Abdul Rauf who refuses to acknowledge Hamas as a terrorist organization, which is how the U.S. government classifies the group. The imam also has also been quoted as saying U.S. foreign policy was in part responsible for the 9/11 attacks.

Still it is important to try and build bridges. In the interest of fostering tolerance and friendship, right-wing pundit, Greg Gutfeld, proposes to open a gay bar next door to the Ground Zero mosque! Gutfeld said he visited the website for the proposed Ground Zero mosque, Cordoba House, and read that it’s mission was to encourage tolerance and dialog. So Gutfeld believes a Ground Zero gay bar right next door would serve the same purpose.

In a famous letter to all Christian nations, Muhammad wrote, "Christians are my citizens; and by God! I hold out against anything that displeases them." He concluded the letter with a firm reminder, "No one of the nation of Muslims is to disobey this covenant till the end of the world."

Of course, the writings of Muhammad are open to cherry pricking and this one is an out of reach fruit for most Muslim countries.

Tuesday, August 10, 2010

Time and again American films seem to suggest that the God that Americans worship is called 'Freedom'. I guess it stems from the American Revolution and the idea that freedom from British rule was the aim, especially as it was so close in time to the French Revolution which had as its slogan, "Freedom, Equality and Brotherhood".

I'm not sure how well this idea fits with Christianity. To be sure, the American Constitution guarantees freedom of religion, but how can religion be free when religions themselves are so exclusive? Since Islam regards changing one's religion from Islam as a crime punishable by death, there can't be much freedom there. In fairness, the Constitution didn't envisage anyone choosing to be a Muslim; rather it gave people freedom to be Presbyterian, Congregationalist, Episcopalian, Lutheran, Baptist or even Catholic.

However, Christianity is often criticised for its exclusivity. Tim Keller quotes two young New Yorkers, "Christians believe that they have the absolute truth that everyone has to believe - or else. That endangers everyone's freedom." and "A one-Truth-fits-all approach is just too confining. The Christians I know don't seem to have the freedom to think for themselves. I believe that each individual must determine truth for him- or herself."

Emma Goldman called Christianity, "The leveller of the human race, the breaker of a man's will to dare and to do; an iron net, a straitjacket which does not let him grow or expand."

Modern man does not believe in any absolute truth, he thinks of truth as something that you have to work out for yourself.

Thus at the end of the 2004 movie I, Robot, the Robot, Sonny, says to Detective Spooner, "Now that I have fulfilled my purpose, I don't know what to do."Spooner replies, "I guess you'll have to find your way like the rest of us, Sonny. That's what it means to be free." Even the Supreme Court has enshrined this view in Law: The heart of Liberty is to define one's own concept of existence, of the meaning of the universe, and the mystery of human life. (Planned Parenthood v Casey)

Michel Foucault, the French philosopher wrote "Truth is a thing of this world. It is produced by multiple forms of constraint and that includes the regular effects of power." Some have extended this idea to suggest that all truth claims are the effect of the exertion of power - truth comes out of the barrel of a gun. This really is Orwell's Ministry of Truth stuff. And of course it doesn't work. North Korean propaganda that they have the best health service in the world doesn't make it so. They still have a high infant mortality rate.

The assertion that all truth is a power play falls prey to its own assertion since that assertion would consequently also be a power play. If, on the other hand, like Freud, you assert that all truth-claims about religions and God are just psychological projections to deal with your guilt and insecurity, then Freud's assertion is caught in the same tea strainer. It is clearly impossible to proceed in this post-modernist way. Something has to be true and other things untrue.

The exclusivity of Christianity is said to be inconsistent with the ideas of a liberal democracy. Many urban neighborhoods contain residents from different races and religions who nonetheless live and work together as a community. All that is required is for them to respect each others' rights and privacy and to work for equal access to jobs, education and political decision making. Common moral beliefs are not necessary. But this is an oversimplification. A liberal democracy must assume a preference of individual to community rights, a division between public and private morality, and the sanctity of personal choice. These beliefs are foreign to many cultures. The idea of inclusive community is an illusion. Every community holds beliefs that create boundaries, including some and excluding others from its circle. Christianity is no different from any other set of beliefs in this respect. If a Gay/Lesbian Society had a Secretary who came out at a meeting with, "I have just had a religious experience and I now believe homosexuality to be a sin" she would almost certainly be expelled from the Society. Would anyone then accuse the the Society of exclusivity? Every community has boundaries. We might accuse Christians if they are rude or unkind to unbelievers, but hardly for maintaining boundaries to their membership.

Others accuse Christians of being culturally rigid. This is so laughable as to hardly be worth considering. It is an accusation that might be made of Muslims, but Christianity grew up in a Jewish context, quickly spread throughout the Roman Empire and then later spread to the barbarians of Northern Europe. Later it became dominated by Europeans and North Americans, but today most Christians live in Asia, Latin America and Africa.

In 1900 Christians comprised 9% of the African population and Muslims 36% today it is 44% and since the 1960s they number more than the Muslims. In China since the Western missionaries left in 1947 there has been explosive growth even among members of the Communist Party, so that it is projected that by 2040 there will be 1.5 billion Christians. In South Korea in the past 50 years an infinitesimal proportion has grown to 49% of the population. Christianity is the most culturally diverse of all religions. Secularism and capitalism are far more destructive of local culture.

Freedom cannot be defined in negative terms such as the absence of confinement or constraint. In fact, constraint is often the means to liberation. To express yourself on the piano you need to constrain yourselves to years of practice. Someone has estimated that to be really good at anything, be it violin playing or surgery, you need 10,000 hours of practice. However, all the hours of practice in the world will not turn a 5 ft 3 inch basketball player into a world beater. There are other constraints to his freedom. On the other hand there are many people in our society who are pursuing careers that pay well but do not really fit their talents. Such careers truly are straitjackets.

Disciplines and constraints only liberate us when they fit with the true reality of our nature and capacities. You do not free a fish by putting on your lawn, but when it is disciplined by the constraints of the water it finds freedom and its life is enhanced. Likewise in our lives freedom is not so much the absence of constraints, but a matter of finding the right ones for our nature.

One of the most frequent assertions by moderns is that every person has to define right and wrong for himself, but when asked if there is not someone in the world right now doing things that they think ought to be stopped no matter what they personally thought about the correctness of their behaviour, they would always answer, "Yes, of course." Few people would condone female circumcision on the grounds that it is what is believed in such and such society to be right for women.

Does this not point to the fact that there is out "there" some sort of universal morality?

Love is the ultimate freedom but it is terribly constraining. Françoise Sagan , the French novelist, was asked whether in what she called her satisfying life she had all the freedom she wanted, replied, "I was obviously less free when I was in love."

To experience the joy and freedom of love you must give up some personal autonomy. Love limits your options. But here is the paradox: human beings are most alive and free in relationships of love.

Freedom is not the absence of limitations and constraints, but it is the finding of the right ones that fit with our nature. Lovers accept mutual constraints.

But isn't loving God a one-way sacrifice? We do all the adjusting?

This may be true in some religions, but it is not true for Christianity. God has adjusted to us in his incarnation and atonement. Jesus accepted the limitations of humanity and became vulnerable to suffering and death. On the cross he submitted to our sinful condition and paid our penalty. If he did this for us, what would we not do for him? As Paul says in 2 Corinthians 5:14, "The love of Christ constrains us."

Is it easy to love God? It is for those who do so. Is it easy to love my wife? Nothing could be easier. When you love someone, no sacrifice is too much, no gift too costly, no service too demeaning. Loving Jesus is not giving up freedom. It is finding freedom in him.

I had a bad day last Tuesday, spending most of the time asleep on the couch and hardly eating, but since then each day has been an improvement on the one before; so much so that I was able to join my wife on a trip to the supermarket and to go to church of Sunday for the first time in two months. We have been able to watch the service on the Internet, but it isn't quite the same as actually being there.

I'm getting closer to my fighting weight. I tipped the scales this morning at 180 pounds. Before I got ill this time I was 200 pounds and when I left hospital I was 177. However, when I compare my thigh muscles with those of my elder son who recently cycled from Brighton to London for charity, I can see where the weight has gone from.

All my children are to some extent athletic. My older daughter was Dorset Champion for gymnastics floor exercises, and my younger daughter Bournemouth champion at long jump. My older son was Dorset triple jump champion and Bournemouth 100 metres champion. His record for the triple jump stood for 17 years before it was beaten. My younger son was Bournemouth 200 metres champion and represented Dorset at both cricket and Rugby. He still plays cricket and soccer to a good standard, is top of the works leader board at golf, and enjoys surfing, snowboarding and cycling as hobbies.

You might say that we are a sporty family. Where does it come from? My father played cricket at county second XI level and my father-in-law boxed a bit. My own sporting prowess was curtailed by a late puberty. At 15 I was the second smallest boy of my year at school. Although, I had been quite a fast runner at 10 and 11, by the time I thought to enter school sports I got my timing wrong. There were always boys who were faster than I was in the sprints, but when a boy who was definitely much slower than I won the under-14s hurdles, I thought I had found my event. The problem that I had not realised was that he was three weeks younger than I. In those days the cut off for athletic events was March 31st, so by being born on March 12th I was one of the oldest in my year, while he, being born on April 7th, was one of the youngest in his.

The following year I entered the hurdles myself. I still had not had my growth spurt. The height of the hurdles astonished me. They were about a foot higher than when he had won. Of course, I fell at the first and suffered the ignominy of the headmaster rushing over and disentangling me from the broken hurdle (they were constructed by the woodworking class and looked like proper sheep hurdles rather than the ones you see nowadays in Track and Field. Thus ended my athletic career.

After puberty I did feature in the school first XI for both cricket and football, but aged 17 I snapped my anterior cruciate and had to give up all thoughts of a career in professional sport!

I have been reading a book called Outliers by Malcolm Gladwell. He makes a similar point about the month you are born in affecting sporting success. A survey of Canadian Ice Hockey players shows that the most successful players are born in the winter months: January, February and March. The simple explanation for this is that the cut-off date for age-class hockey is January 1st. so that those who are older in their year at the age of 10, say, have an enormous physical advantage over those born in December. At this age boys get selected for representative teams and thus benefit from the extra coaching and practice that they receive, so that the age bias becomes set in stone.

This same effect is seen in soccer in the UK, where it is always the bigger boys that get selected for representative teams. I remember a couple of lads in my class who were selected for the English under-15 squad. they were large boys who had an early puberty and could kick a football a long way (these were the days of heavy leather boots and heavy leather balls that got water-sodden when it rained).

Although this was a grammar school with high academic achievement, neither lad was a star in the classroom. Neither progressed in professional sport and one became a hod-carrier and the other left school after becoming a father at the age of 16.

The book is a fascinating read and I may quote from it again. After last week finding that statistics perform better than experts, you won't be surprised to find that succes is related less to ability than to happenstance.

Saturday, August 07, 2010

Although the British government has promised to crack down on immigration, it can do nothing about members of the European Union coming to settle here. We have welcomed many French and Germans and Scandinavians who have found well-paid jobs in the city of London. But therein lies the rub. The UK could have given passports to 2.25 million Hong Kong Chinese or several billion Indians on the basis that they were former members of the British Empire, but in order not to be tarred with the racist brush, in excluding these it also excluded many Australians, Canadians, New Zealanders and Rhodesians who had ethnic ties here. Not every country has the same sensitivities.

At the heart of this scam, which is making a complete mockery of our immigration policy – more so than it already has – are two countries, Romania and Bulgaria. They are handing out passports to ethnically linked groups or minorities outside their borders. The President of Romania has thanked 2 million Romanians now living in Britain for sparing the bankrupt Romanian benefits system and actually sending wages home to impoverish the British and help the Romanian economy. Now Hungary plans to do the same, as of January.

The main beneficiaries are citizens of Moldova, Macedonia, Serbia, Ukraine and Turkey - about 4.7 million people with living standards at a fraction of the EU average. All are eligible for EU citizenship under passport giveaway programs.

Spain enacted legislation in January 2009 giving even the grandchildren of Spaniards whose ancestors left due to political or economic hardship caused by the Civil War the right to obtain passports from Madrid - and the response has been huge. Spanish foreign ministry figures from January indicate that over the first full year of the law, there were 161,463 applications - 95 percent from Latin American countries. So far, 81,715 have been granted. Total Latin American numbers are unavailable - but the Spanish foreign ministry has extended the window for applications by another year to December 2011, due to what it calls "overwhelming demand." In Cuba alone, nearly 82,000 people have applied for Spanish citizenship and 36,415 have received it as of 30 June, clearing the way for the lengthy and expensive process of obtaining permission to travel abroad - or leave permanently. Venezuela's Spanish consulate has handed out more than 35,000 passports so far this year. The number of Mexicans who could qualify is unknown, but 150,000 are estimated to be eligible. Of those, more than 14,000 people have been given Spanish citizenship and huge lines of passport-seekers form every day.

Then there are more than 2.6 million people of Italian origin - most of them also in Latin America – who already hold Italian passports. And, like Spain, Portugal grants passports to children and grandchildren of emigrés - most of them in sprawling Brazil, home to 200 million people.

Getting an EU passport and access to its generous benefits system is like winning the lottery. There must be a stop or there will be riots in the streets.

This is the beach at Pass Christian, Mississippi after cleaning. Normally, it would be covered with sun-worshippers. It isn't Jaws keeping them out of the water, but Obama-hype.

The volume of the Gulf of Mexico is 2,424,000 cubic kilometers, or 6.43 * 10^17 US gallons. The volume of oil spilt is estimated at 20m gallons to 50m US gallons; let's take the maximum, 5 * 10^7 gallons. That's one part of oil to 1.29 * 10^10 parts of water.

The volume of the Thames at mid tide between Teddington and Gravesend is about 2.4 * 10^7 cubic metres (633 * 10^7 US gallons, or 127 times the total volume of the BP oil leaked). To replicate the 'environmental disaster' the Septics are claiming, one would therefore have to empty 1.87 litres of engine oil into the river.

There was some oil on the beaches, however, if the U.S. TV news crews had returned just three days after their original visit, they would have seen that the black morass had already been removed by some of the 20,000 clean-up workers hired by BP.

The workers are still there - only now they are using toothbrushes to sift out even the tiniest particles of oil.

We are now seeing a backlash against the hype that suggested that this was the worst environmental disaster ever. It began when Time magazine's environmental writer voiced the near-heretical proposition: that the effects of the Deepwater Horizon disaster on April 20 had been massively hyped. This article was largely based on the opinions of Professor Ivan van Heerden, a brilliant but controversial marine scientist fired by Louisiana State University after publishing a book about Hurricane Katrina that said cataclysmic flooding was inevitable because the protection given to the coast was wholly inadequate. (No true word ever goes unpunished)

Emboldened by the academic’s willingness to go against the accepted wisdom, other leading scientists have concurred, with similar views being expressed in the influential New York Times and Washington Post (not known for their extreme right-wing views).

The spill from the Exxon Valdez (owned by an American company) in Alaska though smaller was a much more severe ecological disaster. The area’s ecology was devastated, and an estimated 250,000 birds and 2,800 otters died, plus hundreds of seals and at least 22 killer whales. The Gulf spill has so far accounted for some 1300 birds, 17 sea turtles and 3 dolphins. Reports suggest that fish stocks in the Gulf have actually increased because the fisherman have been forced to hold off.

It is the last refuge of a politician in trouble to blame foreigners. BP (no longer for more than a decade "British" Petroleum) merged with Amoco and it is the old Amoco operation in the Gulf that was responsible for the spill. The company is almost equally owned by British and American pension funds. The fall in the share price induced by Obama's xenophobic reaction has hit ordinary American and British pensioners equally hard. I don't have a vote in American elections, but many of my readers do.

Eight foreigners and two Afghans have been found shot dead next to abandoned, bullet-riddled vehicles in north-eastern Afghanistan. Six Americans, a German and a Brit, who formed part of an eye surgery team taking aid to poor Afghans were gunned down along with two Afghan interpreters. A third Afghan was spared because he called out, "I'm a Muslim," and recited parts of the Koran. The Taliban have claimed responsibility and have said that they were doing it because these were Christian missionaries.

The government of Afghanistan have claimed that it was a simple robbery.

Some of my best friends are Muslims and they will be as appalled by these murders as I am. No doubt it is part of the culture and not just the religion, but Afghani culture has already been contaminated by Western technology. Left to themselves these people would not have high explosive, machine guns or rocket propelled grenades. Merely abandoning them to their fate is not an answer. Jesus told his disciples that in villages where they were not welcome they should shake off the dust from their feet and go elsewhere. I don't think that is an option today. We have already seen on 9/11 that these people are not prepared to be troglodytes for ever. Leave them alone and they will attack us.

Unfortunately, the only option we have is to drive them back into their holes and then put the ferrets down after them.

Friday, August 06, 2010

There are now only two secondhand bookshops in the Bournemouth/Poole conurbation, a city of half a million people. In part this is due to the Internet. You can buy any number of used books at Amazon market place. In part it is due to Charity shops, of which there are scores, who all seems to have a secondhand book department.

One of the secondhand book dealers came around last evening to look at some 500 books I want to dispose of. He wasn't interested. He recognized that they were all good and interesting books in good condition, but he had no space on his shelves. Indeed he told me that he gives 500 books away to Oxfam every week.

I am afraid I shall have to follow his example though my charity of choice is the British Heart Foundation - my mother has just been taken into hospital with atrial fibrillation at the age of 90.

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About Me

Born in Worcester, England 1943; school at Farnborough, Hampshire 1954-62; University 1962-7 and junior doctor posts 1967-74 in Bristol; Consultant Haematologist Bournemouth 1974-2003; Professor of Immunohaematology Southampton 1986 to present. Honorary Consultant Haematologist Kings College Hospital, London, 2004-present. After 5 years of working part time researching, writing, reviewing, editing, speaking, sitting on committees, advising, answering questions and thinking, I now think of myself as fully retired apart from my role as Editor in Chief of the medical journal Leukemia Research. I was awarded the Binet-Rai medal for outstanding research in CLL in 2002 and this has been my most sucessful area of research, but I have also made important contributions in the fields of apheresis, stem cell transplantation, myeloma, myelodysplastic syndrome, antibody therapy, cytokine therapy and DNA vaccines. I was once mascot for Aldershot Town Football. Club. Married to Diane for 44 years. Four children, Karen, Richard, Angela and David.